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ObjectivesRheumatoid arthritis (RA) is associated with an increased risk for osteoporosis and osteoporotic fractures. Since the treatment of RA has improved significantly in recent years, we can expect RA-associated osteoporosis to decrease with good disease control. Therefore, we conducted a retrospective study to investigate whether the frequency of osteoporosis and osteoporotic fractures has changed during 24 years in RA.MethodsWe analysed the data of 1.086 RA patients from the time of the first osteological assessment with bone mineral density (BMD) measurement and collection of osteologically important data during the years 1996 and 2019 at our clinic. According to the treatment period, the patients were divided into cohort 1 (investigation between 1996 and 2004; n=539) and cohort 2 (investigation between 2005 and 2019; n=547). The data of the two cohorts were compared, and predictors of BMD were analysed by linear regression analysis.ResultsPrevalence of osteoporosis (28.3% vs 48.4%; p<0.001) as well as osteoporotic peripheral fractures (11.5% vs 21%; p<0.001) and vertebral fractures (6.6% vs 10.9%; p=0.011) were significantly lower and treatment with biologicals (19.7% vs 5.0%; p<0.001) significantly more common and glucocorticoid use was significantly less common (p=0.005) in cohort 2. In RA patients with a disease duration of more than 2 years, BMD was significantly higher under treatment with biologicals (p<0.001) despite increased cumulative glucocorticoid dosages (p<0.001).ConclusionOur study showed a significant decline in osteoporosis and osteoporotic fractures in RA for 24 years. This positive effect is associated with the more frequent use of biologicals in the years between 2005 and 2019.

The aim of our study was to compare the significance of risk factors for osteoporosis according to gender and menopausal state in patients with rheumatoid arthritis (RA). Bone mineral density (dual X-ray absorptiometry), cumulative glucocorticoid dose, age, disease duration, body mass index (BMI) and parameters of disease activity and bone turnover were registered in 343 postmenopausal women, 100 premenopausal women and 108 men with RA. Osteoporosis was found in a significantly higher percentage in postmenopausal women (55.7%) and in men (50.5%) in comparison with premenopausal women (18%; P  < 0.001). The following risk factors for osteoporosis were found: older age, low BMI and high cumulative glucocorticoid dose in postmenopausal women, low BMI and high cumulative glucocorticoid dose in men and low BMI in premenopausal women. There is a very high prevalence of osteoporosis not only in postmenopausal women but also in men with RA. Osteoporosis risk factors are strongly dependent from gender and menopausal state.

Aims The BioBone consortium aims to validate circulating CD8 + TEMRA cells as a prognostic biomarker for predicting impaired fracture healing outcomes in a prospective, blinded, multicenter clinical study. The primary performance parameters are the pre-operative identification of at least 30% of patients who ultimately experience impaired healing at the first clinical endpoint, with a specificity greater than 90% to minimize the false-positive rate. Methods BioBone is a prospective, blinded, multicenter biomarker validation study designed to assess the prognostic value of circulating CD8 + TEMRA cells in fracture healing. A total of 640 patients aged 18 to 80 years with fractures of the humeral diaphysis, radial and/or ulnar diaphysis, femoral neck, trochanteric femur, femoral diaphysis, distal femur, proximal tibia, tibial diaphysis and distal tibia will be enrolled. The study is powered to validate the target assay performance and accounting for 6–7 potential confounders at an expected incidence of 10% impaired healing. Biomarker levels will be measured pre- and post-operatively using flow cytometry (FC) and patients will be monitored for one year. The primary endpoint is fracture healing status at 17–19 weeks (normal healing or delayed healing), while the secondary endpoint evaluates healing at nine months (delayed healing or pseudarthrosis). Fracture consolidation will be assessed through radiographs or computed tomography (CT) scans in conjunction with clinical assessments such as range of motion and weight-bearing capacity. Key outcome measures include radiographic analysis (RUST/RUSH scores), functional and patient-reported outcomes (e.g. weight bearing ability, range of motion, and the SF-36 questionnaire), as well as socioeconomic parameters (e.g. work capacity, rehabilitation needs, mobility). The predictive performance (sensitivity, specificity, NPV, PPV) of the biomarker will be determined in a prospective, double-blinded analysis, where CD8 + TEMRA blood levels are measured prior to surgical treatment and healing status at clinical endpoints is assessed by independent observers. Additional immunological examination and in vitro analysis of blood and fracture hematoma samples will further investigate the mechanism of action of CD8 + TEMRA cells in impaired human bone regeneration. Conclusion The BioBone study will validate the suitability of CD8 + TEMRA cells as a prognostic marker for impaired fracture healing and their integration into routine clinical practice. The results could have a global impact by incorporating immune-based prognostic tools into clinical workflows, paving the way for precision medicine approaches in trauma care. The BioBone study is funded by the German Federal Ministry of Education and Research (BMBF).

Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme in prostanoid biosynthesis and is involved in tumor progression. We investigated expression of COX-1 and COX-2 in cell lines and tumors from ovarian carcinomas. Expression of COX-2 mRNA and protein was detectable in three of five ovarian carcinoma cell lines and was inducible by interleukin-1β or phorbolester in a subset of cell lines. Prostaglandin E 2 (PGE 2) production could be inhibited by the selective COX-2 inhibitor NS-398. In malignant ascites of ovarian carcinomas significantly increased levels of PGE 2 were found compared to other carcinomas or nonmalignant ascites ( P = 0.03). We investigated expression of COX-2 by immunohistochemistry in 117 ovarian surface epithelial tumors. Expression of COX-2 was detected in 42% of 86 ovarian carcinomas and in 37% of 19 low malignant potential tumors, but not in 12 cystadenomas or 2 normal ovaries. Expression of COX-1 was detected by immunohistochemistry in 75% of 75 invasive ovarian carcinomas and in 75% of 16 low malignant potential tumors, whereas 2 samples from normal ovaries and 8 cystadenomas were positive for COX-1. In univariate survival analysis of invasive carcinomas, expression of COX-2 was associated with a significantly reduced median survival time (log rank test, P = 0.04). For patients younger than 60 years of age, this association was even more significant ( P < 0.004). In contrast, expression of COX-1 was no prognostic parameter ( P = 0.89). There was no significant correlation between COX-2 or COX-1 expression and other clinicopathological markers. In multivariate analysis expression of COX-2 was an independent prognostic factor for poor survival (relative risk, 2.74; 95% CI, 1.38 to 5.47). Our data indicate that COX-2 expression is an independent prognostic factor in ovarian carcinoma. Based on the results of this study, it would be interesting to investigate whether ovarian carcinoma patients with tumors positive for COX-2 would benefit from treatment with selective COX-2 inhibitors.

Background For the treatment of colorectal cancer, the S3-Guideline of the German Guideline Program in Oncology supports clinical decision-making. Centers certified by the German Cancer Society are required to implement the guideline recommendations as comprehensively as possible. When guidelines provide insufficient or ambiguous evidence, heterogeneity of treatment preferences is likely to emerge across individual centers. The aim of this study is to describe the preferences of the centers’ tumor boards for treatment decisions when clear, evidence-based guideline recommendations are lacking. Methods To investigate the tumor boards’ preferences for different treatment options, an anonymous online survey was conducted among 314 certified colorectal cancer centers. The survey included seven visceral oncological and nine visceral surgical case vignettes. Centers were asked to discuss the vignettes in the tumor board or, alternatively, delegate them to an appropriate physician representatively speaking for the tumor board. The responses were analyzed descriptively and normalized entropy estimates (NE) were calculated for each vignette. Results A total of 123 centers (39%) responded to the survey. For oncological cases without clear guideline recommendations, substantial heterogeneity (NE: 0.39–0.71) in treatment preferences was observed. For instance, opinions varied widely for UICC II pT4a colon cancer. In this situation, 28% of centers would prefer fluoropyrimidine monotherapy, 39% oxaliplatin-based combination therapy and 33% no adjuvant chemotherapy at all. Surgical vignettes showed a preference for laparoscopic and robotic approaches, with variations based on tumor location (NE: 0.46–0.67). Importantly, in case of a clear evidence-based guideline recommendation, treatment preferences did not differ considerably between hospital sites. Conclusions In prototypical case vignettes without evidence-based guideline recommendations, pronounced heterogeneity of treatment preferences between centers was found. Reconstructing these treatment preferences can contribute to enhancing the quality of evidence derived from observational studies. This seems especially important in the context of clinical questions that cannot be assessed in randomized trials; clinical routine data represent an adequate resource for evidence generation in these scenarios. Trial registration After conducting this study, the main study was registered in the German Clinical Trials Register (DRKS) on October 4, 2024 under study No. DRKS00034650.

Zusammenfassung Hintergrund Primäre maligne Krebserkrankungen des Ösophagus und des ösophagogastrischen Übergangs sind prognostisch ungünstige Krebserkrankungen. Das Ziel dieser Arbeit ist es, für den aktuellsten Zeitraum 2019–2022 bundesweite Inzidenzen dieser Krebserkrankungen sowie die absoluten 5‑Jahres-Überlebenswahrscheinlichkeiten zu schätzen. Material und Methoden Wir schlossen alle inzidenten Krebsfälle des Ösophagus (ICD-10: C15) und des ösophagogastrischen Übergangs (ICD-10: C16.0) aller Krebsregister in Deutschland der Jahre 2019–2022 ein. Wir ermittelten rohe und altersspezifische Inzidenzraten sowie altersgruppenspezifische durchschnittliche jährliche Neuerkrankungszahlen dieser Erkrankungen. Wir ermittelten die absoluten 5‑Jahres-Überlebenswahrscheinlichkeiten mittels Periodenansatz für die Periode 2018–2022 für ausgewählte Krebsregister. Ergebnisse Insgesamt wurden 30.171 Patienten mit Ösophaguskrebs (davon 23,1 % Frauen) und 17.905 Patienten mit Krebs des ösophagogastrischen Übergangs (davon 22,5 % Frauen) registriert. Die Inzidenzrate pro 100.000 Personenjahre des Zeitraums 2019–2022 betrug für den Ösophaguskrebs 14,1 und 4,1 für Männer bzw. Frauen. Die korrespondierenden Inzidenzraten für Krebs des ösophagogastrischen Übergangs betrugen 8,4 und 2,4. Die absoluten 5‑Jahres-Überlebenswahrscheinlichkeiten unterschieden sich zwischen Männern und Frauen nur wenig. Sowohl im ersten Jahr als auch in den ersten 5 Jahren nach Diagnose von Ösophaguskrebs bzw. Krebs des ösophagogastrischen Übergangs zeigte sich sowohl bei Männern als auch bei Frauen, dass die Sterblichkeit bei Krebserkrankungen des ösophagogastrischen Übergangs geringer war als beim Ösophaguskrebs. Diskussion Die ermittelten Inzidenzraten beruhen auf den Krebsregisterdaten aller Bundesländer in Deutschland, sodass auf spezifische Schätzverfahren für Deutschland insgesamt verzichtet und Selektionseffekte vermieden werden konnten. Wir präsentieren in dieser Übersichtsarbeit eine Zusammenfassung grundlegender Maßzahlen zur Häufigkeit von bösartigen Neubildungen des Ösophagus und des ösophagogastrischen Übergangs und der Prognose von Patienten mit diesen Krebserkrankungen.